Obesity is a serious and growing public health problem in this country and around the world. There is a continuing need for investigators with the knowledge of and experience with a range of physiological and behavioral methods to translate new information from studies in animals into new insights in humans through the performance of controlled studies in human subjects. This application is designed in a small way to address this need. The applicant is a mid-career investigator with experience in both animal and human studies in the areas of dietary fat metabolism, insulin resistance, and body weight regulation who is requesting 5 more years of support to 1. continue physiological studies in human subjects conducted in the over and underfed conditions to explore how the body senses nutrient balance and how biological/behavioral responses to positive and/or negative energy balance relate to weight gain. 2. To use his experience in patient oriented research (POR) to continue to mentor junior investigators in their studies of lipid metabolism, insulin resistance, hunger/satiety, exercise, weight gain/loss and related areas. 3. To facilitate interactions and experimental collaborations between established basic researchers working primarily in vitro with junior investigators performing physiological studies in human subjects. 4. To continue to devote some administrative time to activities that promote the professional development of junior investigators and provide the opportunity for these individuals to consider a career in POR. During the previous period of support the applicant was awarded a new RO1 that is supporting a prospective longitudinal cohort study of thin and obesity prone individuals to see if physiological and behavioral responses to short term overfeeding predict subsequent weight gain. In addition, 6 of the 11 post-doctoral fellows that he has worked with during the period of support have received K awards and 2 have received individual NRSA awards. Two junior investigators that he has mentored have received individual RO1 awards and the company that he provides technical support for received an SBIR.